Mastoparan, a Peptide Toxin from Wasp Venom Conjugated Fluvastatin Nanocomplex for Suppression of Lung Cancer Cell Growth

Abstract

Lung cancer has a very low survival rate, and non-small cell lung cancer comprises around 85% of all types of lung cancers. Fluvastatin (FLV) has demonstrated the apoptosis and suppression of tumor-cell proliferation against lung cancer cells in vitro. Drug–peptide nanoconjugates were found to enhance the cytotoxicity of anti-cancer drugs. Thus, the present study aimed to develop a nanocomplex of FLV with mastoparan (MAS), which is a peptide that has membranolytic anti-tumor activity. The nanocomplex of FLV and MAS (MAS-FLV-NC) was prepared and optimized for particle size using Box–Behnken design. The amount of FLV had the highest influence on particle size. While higher levels of FLV and incubation time favored higher particle size, a higher level of sonication time reduced the particle size of MAS-FLV-NC. The optimum formula of MAS-FLV-NC used 1.00 mg of FLV and was prepared with an incubation time of 12.1339 min and a sonication time of 6 min. The resultant particle size was 77.648 nm. The in vitro cell line studies of MAS-FLV-NC, FLV, and MAS were carried out in A549 cells. The IC50 values of MAS-FLV-NC, FLV, and MAS were 18.6 ± 0.9, 58.4 ± 2.8, and 34.3 ± 1.6 µg/mL respectively, showing the enhanced cytotoxicity of MAS-FLV-NC. The apoptotic activity showed that MAS-FLV-NC produced a higher percentage of cells in the late phase, showing a higher apoptotic activity than FLV and MAS. Furthermore, cell cycle arrest in S and Pre G1 phases by MAS-FLV-NC was observed in the cell cycle analysis by flow cytometry. The loss of mitochondrial membrane potential after MAS-FLV-NC treatment was significantly higher than those observed for FLV and MAS. The IL-1β, IL-6, and NF-kB expressions were inhibited, whereas TNF-α, caspase-3, and ROS expressions were enhanced by MAS-FLV-NC treatment. Furthermore, the expression levels of Bax, Bcl-2, and p53 strongly established the enhanced cytotoxic effect of MAS-FLV-NC. The results indicated that MAS-FLV-NC has better cytotoxicity than individual effects of MAS and FLV in A549 cells. Further pre-clinical and clinical studies are needed for developing MAS-FLV-NC to a clinically successful therapeutic approach against lung cancer.

Cytotoxicity of polybia paulista wasp crude venom on the tumor cell lines HeLa, HRT-18, jurkat, and K562

“…When comparing these data with the literature, it can be observed that the response of Jurkat cells to the crude venom of Polybia paulista wasp differs from that found for Brazilian Journal of Development, Curitiba, v.10, n.1, p. 696-707, jan., 2024 concentrations of 5 µg and 10 µg of crude venom from Apis mellifera on HL-60 cells, which resulted in an increase in cells in the S phase and a decrease in cells in the G1 phase (Lee et al, 2007). Conversely, a study on cell cycle analysis conducted by Alhakamy et al (2021) showed that synthetic mastoparan was able to increase the number of cells in the G0/G1 and G2/M phases in an alveolar adenocarcinoma cell line (A549), demonstrating the ability of this peptide to cause cell cycle arrest.…”

Function and Mechanism of Antiviral Wasp Venom Peptide Protopolybia-MP III and Its Derivatives against HSV-1

“…At present, the AVP database (http://crdd.osdd.net/servers/avpdb) (accessed on 29 December 2023) contains 2683 targeted AVPs related to more than 60 antiviral medicines that have great potential to become antiviral drugs [6]. Mastoparan family peptides derived from wasp venom exert various pharmacological effects, including bacteriostasis, immune regulation, and antitumor effects [16][17][18]. However, the antiviral function of natural wasp venom peptides has not been reported.…”

“…Wasp venom contains a variety of bioactive substances, among which Mastoparan family peptides are a class of small-molecule peptides with the highest content and the largest number of members in wasp venom [ 15 , 16 ]. Previous studies have shown that Mastoparan family peptides are an important class of lead drug peptide molecules that have various pharmacological effects, such as inhibiting bacterial infection, regulating the immune system, and providing antitumor activity [ 16 , 17 , 18 ]. However, the antiviral functions of natural wasp venom Mastoparan family peptides are still unknown.…”

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

“…or subcutaneously (s.c.); Table ). M7-NH2 is a mucosal adjuvant and mast-cell-activating oligopeptide (Ile-Asn-Leu-Lys-Ala-Leu-Ala-Ala-Leu-Ala-Lys-Ala-Leu-Leu-NH2) which originated from the mastoparan peptide toxin found in wasp venom. − …”